Reliable, Reportable Data with Analytical Quality by Design Approaches

By September 10, 2021


There’s a significant paradigm shift and it’s drastically changing the way pharmaceutical organizations and their partners achieve reliable, reportable data. The route to drug approval requires a multitude of underlying activities and factors which, if not managed carefully, can have a devastating business impact. While still important, regulatory compliance alone is simply not enough to be able to make critical drug product related decisions.

Analytical Quality by Design: Paradigm Shift for Method Development

Recently, Quality by Design (QbD) principles for drug manufacturing, as described in ICH Q8, are suggested to increase the robustness of analytical methods to generate reliable, reportable data to enable such decisions.

As a response, new upcoming guidance from the US Pharmacopeia called Chapter <1220>, “The Analytical Procedure Lifecycle” and the ICH Q14, “Analytical Procedure Development,” outline and suggest how QbD principles can be applied for risk-based method development and optimization. Commonly referred to as Analytical Quality by Design (AQbD), it is more important than ever to implement such risk-based processes for method development and optimization as the pressures of maintaining quality and ensuring patient safety continue to grow.

Reliable, reportable data: the result of AQbD

Traditional or conventional method development or optimization is often empirical, and the quality of the method is usually not assessed properly.

Under an AQbD approach, the first step is to define and document the intended purpose and required performance of the method in the form of an Analytical Target Profile (ATP). Once the method requirements are fully assessed, risk assessments are performed to determine the right technology capable of meeting the ATP and what parameters, when varied and to what degree, will impact the method’s ability to meet the ATP.

According to Dr. Stephanie Harden, Manager of Global Pharmaceutical Business Development at Waters Corporation: “Having a thorough understanding of how to develop robust methods that are fit for their intended purpose, achieve performance goals, and are linked to the Critical Quality Attributes (CQA) of specific drug products is the new approach.

“The new measure of method success is the output, or reportable result. To achieve a trustworthy result, methods should be well-understood, undergo an upfront risk assessment, and its performance criteria should be specified in terms of accuracy and precision in an Analytical Target Profile (ATP).

“The method should also embody a control strategy designed to mitigate the identified risks and method performance trending should take place throughout the method’s life. In addition, scientists also need access to easy-to-use and high-performing analytical instrumentation. Without the right analytical technologies, executing methods can prove challenging and hinder progress.”

According to Dr. Harden, modern tools and technologies are leading the way in the design of robust, fit-for-purpose methods; enhancing laboratory efficiency, controlling risk, and generating reportable results that enable better decision-making.

Recent software advancements that enable fully automated Design of Experiments (DOE) with MS peak tracking serve as vital tools to support AQbD method development and/or optimization. In conjunction to evaluating the technology that enables the method to meet the ATP, modern LC technologies are being adopted.

AQbD: Benefits beyond reliable, reportable data

The direct result of implementing AQbD for method development is obtaining trustworthy results from a robust method – but there is so much more! AQbD approaches not only support the development of robust methods; they promote method performance monitoring, as well as reduce the need and cost to redevelop and revalidate methods. Such risk-based approaches also increase the success rate of method validation and transfer, improve data quality, increase confidence to communicate with regulators, and reduce regulatory submission inquiries.

Modern technologies and tools to support AQbD implementation

Access additional resources to learn more about how you can leverage modern analytical tools and apply an Analytical Quality by Design approach in your laboratory:


Categories: Pharmaceutical